Engineering an ultra-thin opto-acoustic fibre optic probe for cancer characterisation

Cancer claims the lives of over 450 UK citizens every single day. The best outcomes in patients are seen when early detection of cancerous material is achieved to enable swift delivery of appropriate treatment modalities. To achieve this, additional approaches to enable the assessment of cellular properties that

can differentiate tumour cell from normal healthy cells would be of significant value to cancer detection at earlier stages than those currently detectable today. In particular, the elasticity of cancer cells and healthy cells differ, though the extent of the differences between cell types is not well understood . The heterogeneity of stiffness within tumours (i.e from the core

to periphery) has been identified in a number of studies. Tumour cells undergoing migration and invasion are associated with low-stiffness, which is also found in the hypoxia-associated cancer cells. In addition, high tissue pressure also affects cell stiffness and is inversely correlated to drug delivery, thus impacting the

efficacy of treatments. The recent recognition of the importance of mechanical properties as an indicator of disease state, coupled with the capability of fibre optics and advanced thin film manufacturing techniques means that a compact ultrasound probe is now within reach, paving the way for future in-vivo biopsy.

This proposal will develop new instrumentation to measure the mechanical properties of soft matter like tissues, through the interaction of acoustic interface waves. This novel methodology will enable mechanical characterisation of a range of materials focusing on cancerous tissue to enable classification of healthy

and disease state. I will draw upon many years of experience pioneering spatially resolved acoustic spectroscopy, which has been very successful in characterising hard engineering materials (leading to 10 publications and 1 patent), to develop a new instrument that can be applied to soft materials. This instrument will exploit an

engineered device that can generate an acoustic wave at the interface between the device and the sample and simultaneously detect the velocity of the generated wave. Critically, the method proposed here overcomes a longstanding issue of attenuation in interface wave devices as the generation and detection occur in the same spatial location so long propagation distances

are avoided. The novel transducer substrates enable a suite of deployment options, for instance, I'll be able to use these on a microscope or build them on an optical fibre. In the future it will be possible to embed these sensors in scalpels and small finger probes. The flexibility allows measurements to span a

wide range of length scales - from microns to millimetres - opening a wide range of application areas to target. Bio-mechanics are known to play an important role in cancer and the development of tumours. The proposed technology will enable the observation of single cells and groups of cells through to probing

macroscale tissue and tumours. We will study a range of healthy and cancerous cell lines to determine the variation in the elastic properties of the cell, the influence of therapeutic drugs and how the cells change depending on their environment. This tool will initially be very valuable as a discovery tool in bio-medical research as it will allow new

research avenues in bio-mechanical characterisation. The fibre optic nature of the device means that the future route to in vivo diagnostics is simplified allowing faster adoption of the technique.